Impact of chronic single or combined exposure to bisphenol A and perfluorooctanoic acid on human osteoblast spheroid
By Fiorenza Sella, Christian Giommi, Marta Lombó, and Oliana Carnevali
Environ Pollut
June 4, 2026
DOI: 10.1016/j.envpol.2026.128521
Environmental exposure to endocrine-disrupting chemicals (EDCs) has increased substantially due to widespread industrial activities. Even at low doses, EDCs can interfere with hormonal signaling and affect multiple physiological systems, including bone. Among the most prevalent EDCs are bisphenol A (BPA) and perfluorooctanoic acid (PFOA). Although their individual effects are well documented in vivo and in in vitro 2D models, while the use of 3D bone models and their combined impact on bone tissue remains poorly explored. This study investigated the effects of BPA (50 μM) and PFOA (1 μM), alone or their co-exposure, using human fetal osteoblast (hFOB 1.19) spheroids cultured under osteogenic conditions for 21 days (chronic exposure). These concentrations were selected based on previous in vitro studies and preliminary evidence indicating adverse, yet non-cytotoxic effects, suitable for long-term experiments. Spheroid morphometry, cell viability, extracellular matrix (ECM) deposition, and related protein markers were evaluated. Cell viability was not significantly affected by EDCs exposure. However, morphometric analysis revealed dynamic structural changes throughout the exposure period. At early stages, the combined exposure exerted antagonistic effects on spheroid area, solidity, and roundness. By the end of the 21-day exposure, no evidence of synergistic or antagonistic effects was detected, with co-exposure responses largely reflecting the effects of the individual compounds. BPA and the combined exposure to both EDCs increased COL1A2 protein levels, suggesting a stiffer ECM, despite a concomitant reduction in ECM mineralization. Decreased mineralization was also observed following PFOA exposure. Overall, BPA and PFOA induce toxicity on human osteoblast spheroids highlighting the importance of human 3D models for evaluating chronic and combined EDCs exposure effects on human bone health.
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